Role of nuclear-FGFR1 in Schizophrenia and Ontogenic Genome Programming – A Computational Study

Abstract

Earlier studies from schizophrenia patients have shown that the disorder causes changes in the genome at proneuronal stage – best progenitor cells commit to neural cells. In particular, the mRNA transcriptome nuclear FGFR1 (nFGFR1) was found to be dysregulated. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) derived cerebral organoid from four control and three schizophrenia patients were grown to model the first trimester of in utero brain development. These organoids were tagged to show Ki67 + neural progenitor cells (NPCs) and calretinin interneurons in the cortical plate (CP). Using computational algorithms to detect cells and characterize them, it was discovered that NPCs in schizophrenia modeled organoids abnormally in comparison to those in control organoids. The matured interneurons in the CP showed decreased intracortical connectivity denoted by changes in their orientation.